Age-related effects of sodium arsenite on splenocyte proliferation and Th1/Th2 cytokine production

Cho, Yuri; Ahn, Kyong Hoon; Back, Moon Jung; Choi, Jong Min; Ji, Jung Eun; Won, Jong Hoon; Fu, Zhicheng; Jang, Ji Min; Kim, Dae Kyong

doi:10.1007/s12272-012-0219-3

Cited by 16 publications

(12 citation statements)

References 38 publications

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“…Mitogen induced T-cell proliferative response and cytokine secretion was also found to be suppressed in arsenic exposed population 15 , 19 and in-vitro arsenic exposed human PBMCs 14 , 16 , 17 . Similar response was observed in mouse model 20 – 22 .…”

Section: Introductionsupporting

confidence: 86%

Arsenic exposure impels CD4 commitment in thymus and suppress T cell cytokine secretion by increasing regulatory T cells

Gera

Singh

Mitra

et al. 2017

Sci Rep

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Arsenic is globally infamous for inducing immunosuppression associated with prevalence of opportunistic infection in exposed population, although the mechanism remains elusive. In this study, we investigate the effect of arsenic exposure on thymocyte lineage commitment and the involvement of regulatory T cells (Treg) in arsenic-induced immunosuppression. Male Balb/c mice were exposed to 0.038, 0.38 and 3.8 ppm sodium arsenite for 7, 15 and 30 days through oral gavage. Arsenic exposure promoted CD4 lineage commitment in a dose dependent manner supported by the expression of ThPOK in thymus. Arsenic also increased splenic CD4+ T cells and promoted their differentiation into Treg cells. In parallel, arsenic exposure induced immunosuppression characterized by low cytokine secretion from splenocytes and increased susceptibility to Mycobacterium fortuitum (M. fortuitum) infection. Therefore, we linked arsenic-induced rise in Treg cells with suppressed Th1 and Th2 related cytokines, which has been reversed by inhibition of Treg cells in-vivo using wortmannin. Other parameters like body weight, kidney and liver function, histoanatomy of thymus and spleen as well as thymocyte and splenocytes viability were unaltered by arsenic exposure. Taken together our findings indicated that environmentally relevant dose of arsenic enhanced differentiation of Treg cells which in turn induce immunosuppression in experimental animals.

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Section: Introductionsupporting

confidence: 86%

Arsenic exposure impels CD4 commitment in thymus and suppress T cell cytokine secretion by increasing regulatory T cells

Gera

Singh

Mitra

et al. 2017

Sci Rep

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“…The authors found that at the highest doses of sodium arsenite, T lymphocytes underwent less mitogen-stimulated proliferation when pretreated (in the case of mitogens PHA and Con A) or simultaneously cultured (in the case of mitogen PHA only) with sodium arsenite, similar to results noted by Soto-Peña et al [14] and Kozul et al [60]. Another study by Cho et al [62] found that C57BL/6 splenocytes from young adult female mice exhibited reduced proliferation and IFN-γ production, as well as a non-significant decreasing trend in IL-2 production, when cultured with Con A, and increasing concentrations of sodium arsenite. The same downward trend in IL-2 production with increasing arsenic concentration was also noted for splenocytes cultured with anti-CD3 antibody, and the decrease was found to be significant at the highest dose of arsenic (2 μM).…”

Section: Arsenic Exposure and Immune Responsessupporting

confidence: 70%

Arsenic and Immune Response to Infection During Pregnancy and Early Life

Attreed

Navas‐Acien

Heaney

2017

Curr Envir Health Rpt

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Purpose of Review Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity—including the specific mechanisms in humans—is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life. Recent Findings The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Summary Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines.

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“…A biphasic dose-dependent response was observed following As III or As V exposure of mitogen-stimulated human and bovine PBMC [119], demonstrating As immunosuppressive effects depend on the dose. As markedly suppressed lymphocyte secretion and/or mRNA levels of IFN-γ, IL-4 and IL-10 in different in vitro models [114,116,117]. As III also significantly impaired differentiation of human Th17 cells by repressing their expression and release of IL-17 and decreasing expression of RORγt, which regulates IL-17, through inactivation of JNK/c-Jun pathway [120].…”

Section: In Vitro Studiesmentioning

confidence: 99%

Arsenic immunotoxicity: a review

2013

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Exposure to arsenic (As) is a global public health problem because of its association with various cancers and numerous other pathological effects, and millions of people worldwide are exposed to As on a regular basis. Increasing lines of evidence indicate that As may adversely affect the immune system, but its specific effects on immune function are poorly understood. Therefore, we conducted a literature search of non-cancer immune-related effects associated with As exposure and summarized the known immunotoxicological effects of As in humans, animals and in vitro models. Overall, the data show that chronic exposure to As has the potential to impair vital immune responses which could lead to increased risk of infections and chronic diseases, including various cancers. Although animal and in vitro models provide some insight into potential mechanisms of the As-related immunotoxicity observed in human populations, further investigation, particularly in humans, is needed to better understand the relationship between As exposure and the development of disease.

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Age-related effects of sodium arsenite on splenocyte proliferation and Th1/Th2 cytokine production

Cited by 16 publications

References 38 publications

Arsenic exposure impels CD4 commitment in thymus and suppress T cell cytokine secretion by increasing regulatory T cells

Arsenic exposure impels CD4 commitment in thymus and suppress T cell cytokine secretion by increasing regulatory T cells

Arsenic and Immune Response to Infection During Pregnancy and Early Life

Arsenic immunotoxicity: a review

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